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A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

Trial Information

A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.

Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.

After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.

Inclusion Criteria:

- Diagnosis of 1 of the following:

- B-cell chronic lymphocytic leukemia (CLL)

- Small lymphocytic lymphoma (SLL)

- Must have received 1-3 prior therapies for CLL

- Completed therapy 2-12 months ago

- Prior therapy must have led to a partial response or greater

- No evidence of progressive disease

- ECOG performance status 0-2

- Absolute neutrophil count ≥ 1,000/mm³

- WBC ≤ 5,000/mm³

- Platelet count ≥ 50,000/mm³

- Cytopenia allowed

- Creatinine < 2.0 mg/dL

- Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)

- AST ≤ 2 times normal (unless due to hemolysis)

- No secondary malignancy or other disease that would limit survival to < 2 years

- No history of inflammatory bowel disease unless inactive for > 2 years

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- See Disease Characteristics

- No other concurrent chemotherapy

- No concurrent radiotherapy

- No concurrent dexamethasone or other corticosteroid-based antiemetics

Type of Study:

Study Design:

Outcome Measure:

Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy

Outcome Description:

Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.

Outcome Time Frame:

Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment

Safety Issue:

Yes

Principal Investigator

Leslie Andritsos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00161

NCT ID:

NCT00377104

Start Date:

September 2006

Completion Date:

Related Keywords:

B-cell Chronic Lymphocytic Leukemia

Contiguous Stage II Small Lymphocytic Lymphoma

Noncontiguous Stage II Small Lymphocytic Lymphoma

Stage I Chronic Lymphocytic Leukemia

Stage I Small Lymphocytic Lymphoma

Stage II Chronic Lymphocytic Leukemia

Stage III Chronic Lymphocytic Leukemia

Stage III Small Lymphocytic Lymphoma

Stage IV Chronic Lymphocytic Leukemia

Stage IV Small Lymphocytic Lymphoma

Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Lymphoid

Lymphoma

Name

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

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